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However, current therapies are often limited in efficacy due to poor biocompatible functional materials and the inability to deliver drugs on demand in the pathological joint. Herein, we developed a triple\u2010responsive, nanostructured injectable hydrogel (Cur\/GP\u2010HA) to OA joint microenvironment for synergistic treatment. The Cur\/GP\u2010HA hydrogel was formed by cross\u2010linking hyaluronic acid (HA) with curcumin (Cur)\u2010preloaded, phenylboronic acid\u2010modified generation 3 poly(amidoamine) dendrimers, utilizing the dynamic covalent chemistry between diols on HA and PBA under a physiological pH. This hydrogel exhibited a 3D porous network with excellent injectability and self\u2010healing ability, enabling intelligent Cur release in response to low pH, high reactive oxygen species (ROS) generation, or mechanical compression. Importantly, the constructed Cur\/GP\u2010HA hydrogel removed ROS, promoted the polarization of macrophages, and regulated cytokine secretion to reshape the anti\u2010inflammatory microenvironment. In vivo, intra\u2010articular injection of Cur\/GP\u2010HA hydrogel significantly reduced cartilage erosion, alleviated joint inflammation, and improved subchondral bone integrity. In addition, the synergistic combination of HA lubrication and sustained Cur release provided chondroprotection and anti\u2010wear effects. This work proposes an intelligent injectable hydrogel integrating antioxidant, immunomodulatory, and mechano\u2010responsive protective functions, providing a promising new strategy for OA treatment.<\/jats:p>","DOI":"10.1002\/adfm.75118","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:10:37Z","timestamp":1774595437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Responsive Dendrimer\u2010Hyaluronic Acid Hydrogel With Lubricating and Immunoregulatory Functions for Synergistic Osteoarthritis Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4385-3041","authenticated-orcid":false,"given":"Junjie","family":"Liu","sequence":"first","affiliation":[{"name":"DWI\u2010Leibniz\u2010Institute for Interactive Materials  Aachen Germany"},{"name":"Institute of Technical and Macromolecular Chemistry RWTH Aachen University  Aachen Germany"}]},{"given":"Mengsi","family":"Zhan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Fiber Materials Shanghai Engineering Research Center of Nano\u2010Biomaterials and Regenerative Medicine College of Biological Science and Medical Engineering Donghua University  Shanghai China"}]},{"given":"Haoyu","family":"Huang","sequence":"additional","affiliation":[{"name":"DWI\u2010Leibniz\u2010Institute for Interactive Materials  Aachen Germany"},{"name":"Institute of Technical and Macromolecular Chemistry RWTH Aachen University  Aachen Germany"}]},{"given":"Jianhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Bio\u2010Organic Chemistry Departments of Biomedical Engineering and Chemical Engineering &amp; Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology  Eindhoven The Netherlands"}]},{"given":"Cheng","family":"Ni","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Fiber Materials Shanghai Engineering Research Center of Nano\u2010Biomaterials and Regenerative Medicine College of Biological Science and Medical Engineering Donghua University  Shanghai China"}]},{"given":"Xiaojun","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Fiber Materials Shanghai Engineering Research Center of Nano\u2010Biomaterials and Regenerative Medicine College of Biological Science and Medical Engineering Donghua University  Shanghai China"}]},{"given":"Hannah","family":"K\u00fcttner","sequence":"additional","affiliation":[{"name":"DWI\u2010Leibniz\u2010Institute for Interactive Materials  Aachen Germany"},{"name":"Institute of Technical and Macromolecular Chemistry RWTH Aachen University  Aachen Germany"}]},{"given":"Cong","family":"Song","sequence":"additional","affiliation":[{"name":"Medical Science and Technology Innovation Center Shandong First Medical University  Jinan Shandong China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-6645","authenticated-orcid":false,"given":"Xiangyang","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Fiber Materials Shanghai Engineering Research Center of Nano\u2010Biomaterials and Regenerative Medicine College of Biological Science and Medical Engineering Donghua University  Shanghai China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1825-7798","authenticated-orcid":false,"given":"Andrij","family":"Pich","sequence":"additional","affiliation":[{"name":"DWI\u2010Leibniz\u2010Institute for Interactive Materials  Aachen Germany"},{"name":"Institute of Technical and Macromolecular Chemistry RWTH Aachen University  Aachen Germany"},{"name":"Aachen Maastricht Institute for Biobased Materials Maastricht University  Geleen The Netherlands"}]}],"member":"311","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.09.012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40266\u2010015\u20100330\u20105"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2023.04.015"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926\u2010018\u20100794\u20105"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c00909"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","DOI":"10.1063\/5.0228692","article-title":"Immunomodulatory Hydrogels for Tissue Repair and Regeneration","volume":"12","author":"Liu X. 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